Fluoromethyl-1,1,1,3,3,3-hexafluoroisopropyl ether (sevoflurane) has been widely used as a safe inhalation anesthetic for use. As described in U.S. Pat. No. 4,250,334 (Patent Literature 1), sevoflurane can be synthesized by adding concentrated sulfuric acid and hydrogen fluoride to paraformaldehyde, heating the obtained reaction mixture, and adding 1,1,1,3,3,3-hexafluoroisopropyl alcohol (HFIP) dropwise to the mixture. A substance of interest (i.e., sevoflurane) can be collected together with an unreacted substance (e.g., HFIP) by collecting a gas generated in the reaction system.
Various by-products are generated in the above sevoflurane synthesis reaction. Of these, a by-product that is difficult to separate is bis(fluoromethyl)ether. However, it has been reported that bis(fluoromethyl)ether can be efficiently removed by bringing a reaction mixture of sevoflurane into contact with “Brønsted acid such as concentrated sulfuric acid, Lewis acid, or an acid immobilized to a resin or the like” (Patent Literature 2: JP Patent No. 2786106). Alternatively, bis(fluoromethyl)ether can be efficiently removed by bringing it into contact with zeolite (Patent Literature 3: JP Patent No. 3240043).
In addition, it is known that unreacted HFIP can be efficiently removed by bringing an organic layer containing sevoflurane into “contact with an basic aqueous solution of sodium hydroxide or the like” (Patent Literature 4: JP Patent No. 4087488).
Another by-product contained in sevoflurane is fluoromethyl-1,1,3,3,3-pentafluoroisopropenyl ether (generally referred to as “compound A”). This compound is regarded as a compound that is generated when sevoflurane undergoes a dehydrofluoriation reaction. When sevoflurane is brought into contact with a strong base such as sodium hydroxide, a small amount of this compound might be generated. In addition, it is gradually generated during distillation and purification of sevoflurane (see the following formula).

The compound A itself is a stable compound so that it is not easily degraded even when heated. In addition, it shows pseudoazeotropic behavior together with sevoflurane. For such reason, once the compound A is generated during purification of sevoflurane, it often becomes difficult to separate the compound A from sevoflurane (purification of sevoflurane).
As a technique for solving such problem, JP Patent No. 2786108 (Patent Literature 5) describes attempts made to conduct “distillation and purification under the presence of a degradation inhibitor such as sodium hydrogen phosphate.” It has been revealed that a reaction for degrading sevoflurane into the compound A during distillation can be remarkably inhibited by such technique, and a small amount of the compound A is mainly concentrated in a first distillation fraction so that sevoflurane obtained as a main distillation fraction contains substantially no compound A. As a result, sevoflurane containing the compound A at a level not greater than the detection limit was successfully obtained as a main distillation fraction.